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We aimed to compare the outcomes of COVID-19 Renal Transplant Recipients (RTRs) managed on an ambulatory basis to that of inpatient management.We performed a retrospective study in Lucknow, India, comparing the ambulatory management with the historical cohort managed in the hospital.R RTRs with mild COVID-19 were managed by supervised home-based self-monitoring (HBSM), a strategy to manage this high-risk group on an outpatient basis during the second wave of the pandemic. The primary outcome was the clinical deterioration to a higher severity category among RTRs with mild COVID-19 managed by HBSM compared to hospitalized patients within two weeks of disease onset.Of the 149 RTRs with mild COVID-19, 94 (63%) and 55 (37%) were managed by HBSM and in the hospital, respectively. The proportion of RTRs who clinically deteriorated to a higher severity category (moderate or severe category) was similar among both groups (28.7% versus 27.2%, P=0.849). Among RTRs with clinical deterioration, COVID-19-related death was reported in two patients of the HBSM group and in none of the patients of the hospitalized group. Graft dysfunction was higher in the hospitalized group (7.4% versus 27.2%, P=0.002). Median time to complete clinical recovery (7 days in both groups), secondary bacterial infections (25% versus 33.3%, P=0.41), and the mean decline in EQ-5D score from baseline at six weeks (-6.6 versus-4.3, P=0.105) were found to be similar in both groups.

An attempt was made to develop nutrient rich extruded snacks from lesser utilized protein rich shrimp (Solenocera crassicornis) flour using twin screw extruder. The extruded were in order to fried and packed in to High Density Polyethelene (HDPE). The extruded were analyzed for physical, texture profile, proximate composition and sensory characteristics at the interval of 10 days for 50 days of storage (DOS). The experiment shows the physical property like expansion ratio (mm) and texture profile characteristics such as hardness (gmF) and crispiness (gm) were not affected at the end of storage period. Among the different studies, the product made from rice/shrimp T1 based extruded scored as higher as 5 (out of 5) by sensory evaluation for all attributes. Consequently, all the extruded were maintained the physical properties, nutritional quality and overall acceptability. This research demonstrated that shrimp flour at 15% can be successfully incorporated for development of extruded were: expansion ratio 3.32, 2.75 and 3.06 (mm), crispiness 291, 252 and 210 (gm), protein 12.69, 18.74 and 15.09 (%), enegy value 540, 489 and 524 (Kcal), TPC 0.36, 0.34 and 0.34 (log cfu/gm) in rice T1, wheat T2 and corn T3 based extruded respectively. Overall, the quality assessment of extruded were not changed significantly (P>0.05) throughout study.

Background ALRN-6924 is a stabilized, cell-permeating alpha-helical peptide that mimics the p53 tumor suppressor protein to disrupt p53’s interactions with its endogenous inhibitors, MDM2 and MDMX. ALRN-6924 has been evaluated in > 175 cancer patients and demonstrated single-agent activity and a well-tolerated single-agent safety profile. MDM2 amplification is an oncogenic event found in up to 4% of all cancers. Co-amplification of MDM2 and cyclin-dependent kinase 4 (CDK4), which are co-located on chromosome 12q13, provides the rationale for combined use of the MDM2-inhibitor ALRN-6924 and the CDK4/6 inhibitor palbociclib in this population, and is further supported by enhanced combination activity in preclinical models. Methods This trial is designed to enroll 25 patients with solid tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplifications. Patients have exhausted or are not eligible for other treatment options. ALRN-6924 is given at a dose of 3.1 mg/kg as IV infusion on Days 1, 8 and 15, and palbociclib is given as an oral dose of 100 mg/day on Days 1-21 of every 28-day treatment cycle. The first nine patients enrolled were evaluated for safety and tolerability after completion of one treatment cycle (safety lead-in). Anti-tumor activity is evaluated with imaging every 8 weeks. Results Patient enrollment started in December 2018. As of April 30, 12 patients were enrolled; tumor types include liposarcoma (N = 10), osteosarcoma and glioblastoma (1 of each); 11/12 patients had tumors that were MDM2 and CDK4 co-amplified. The combination was generally well tolerated with transient, self-resolving Grade 3 and 4 neutropenia (N = 7) emerging as the principal but not dose limiting toxicity. Other Grade 3 and 4 adverse events include thrombocytopenia, leukopenia, increased ALT, pulmonary embolism, and fall. An interim analysis of activity and safety (N = 15 patients with ≥2 post baseline CT scans) is scheduled for early September 2019 and the results will be presented. Conclusions The combination of ALRN-6924 and palbociclib at pharmacologically relevant doses is feasible and generally well tolerated. Clinical trial identification NCT02909972. Legal entity responsible for the study Aileron Therapeutics, Inc. Funding Aileron Therapeutics, Inc. Disclosure F. Meric-Bernstam: Honoraria (self): Sumitomo Dainippon Pharma; Dialectica; Advisory / Consultancy: Genentech; Advisory / Consultancy: Inflection Biosciences; Advisory / Consultancy: Pieris; Advisory / Consultancy: Darwin Health; Advisory / Consultancy: Samsung bioepis; Advisory / Consultancy: Aduro; Advisory / Consultancy: Spectrum; Advisory / Consultancy: OrigiMed; Advisory / Consultancy: Debio; Advisory / Consultancy: Xencor; Advisory / Consultancy: Jackson Laboratory; Advisory / Consultancy: Mersana; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Zymeworks; Advisory / Consultancy: Kolon Life Sciences; Advisory / Consultancy: Parexel International; Research grant / Funding (institution): Novartis; AstraZeneca; Taiho; Genentech; Calithera; Debio; Bayer; PUMA; CytoMx; Research grant / Funding (institution): Aileron; Zymeworks; Curis; Pfizer; eFFECTOR; Abbvie; Guardant Health; Daiichi Sankyo; GSK; Travel / Accommodation / Expenses: Taiho; Genentech; Debio; Pfizer. S.G. DuBois: Advisory / Consultancy: Loxo Oncology; Travel / Accommodation / Expenses: Loxo Oncology; Travel / Accommodation / Expenses: Genentech. G.I. Shapiro: Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Merck KGaA/EMD Serono; Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Sierra Oncology; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Pfizer; Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy, Advisory Board: G1 Therapeutics; Advisory / Consultancy, Advisory Board: Roche; Advisory / Consultancy, Advisory Board: Bicycle Therapeutics; Advisory / Consultancy, Advisory Board: Fusion Pharmaceuticals; Advisory / Consultancy, Advisory Board: Astex; Advisory / Consultancy, Advisory Board: Almac; Advisory / Consultancy, Advisory Board: Ipsen; Advisory / Consultancy, Advisory Board: Bayer; Advisory / Consultancy, Advisory Board: Angiex; Advisory / Consultancy, Advisory Board: Daiichi Sankyo; Licensing / Royalties, Compositions and Methods for Predicting Response and Resistance to CDK4/6 Inhibition: Patent pending (work) on palbociclib. M.R. Patel: Research grant / Funding (institution): Aileron Therapeutics, Inc. T. Bauer: Advisory / Consultancy: Ignyta; Guardant Health; Loxo; Pfizer; Moderna Therapeutics; Pfizer; Speaker Bureau / Expert testimony, Speaker’s bureau: Bayer; Research grant / Funding (institution): Daiichi Sankyo; Medpacto; Incyte; Mirati; MedImmune; Abbvie; AstraZeneca; Leap Therapeutics; Research grant / Funding (institution): MabVax; Stemline Therapeutics; Merck; Lilly; GSK; Novartis; Pfizer; Research grant / Funding (institution): Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; Ignyta; Calithera; Kolltan; Research grant / Funding (institution): Principa; Peleton, Immunocore; Roche; Aileron; BMS; Amgen; Moderna; Research grant / Funding (institution): Sanofi; Boehrnger Ingelheim; Astellas; Five Prime; Jacobio; top Alliance; Loxo; Janssen; Clovis; Research grant / Funding (institution): Takeda; Karyopharm; Onyx; Phosplatin; Foundation Medicine; ARMO; Travel / Accommodation / Expenses: Astellas; AstraZeneca; Celgene; Clovis; EMD Serono; Genentech; Lilly; Travel / Accommodation / Expenses: Merck; Novartis; Pharmacyclics; Sysmex. D. Pinchasik: Full / Part-time employment, former Aileron employee: Aileron Therapeutics, Inc. A. Annis: Shareholder / Stockholder / Stock options: Aileron Therapeutics, Inc.; Full / Part-time employment: Aileron Therapeutics, Inc. M. Aivado: Shareholder / Stockholder / Stock options: Aileron Therapeutics, Inc.; Full / Part-time employment: Aileron Therapeutics, Inc. V. Vukovic: Full / Part-time employment: Aileron Therapeutics, Inc. All other authors have declared no conflicts of interest.

The axial instability of the winding conductor is one of the principal modes of mechanical failure in large power transformers. It is caused by axial compressive forces generated by the electromagnetic interaction of the short-circuit current and the radial leakage flux. It is a buckling type of mechanical instability that occurs under compression. Two possible modes of failure in the layer type coil wound with the continuously transposed cable are identified and analyzed in this paper. The critical design loads leading to instability of the individual strands as well as of the whole cable are separately derived. The actual instability threshold of the coil would be the lesser of the two critical loads. For the through-fault integrity of the transformer design, this threshold must be greater than the peak compressive force on the cable under the worst case short-circuit current.

Glioblastoma (GBM) is the most common brain cancer. Resistance to front-line systemic therapy with temozolomide (TMZ) is correlated with O6-methylguanine-DNA-methyltransferase (MGMT) expression. Second-line treatment with bevacizumab has not improved overall survival. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that has MGMT-independent cell-kill activity against GBM cell-lines and cancer stem cells in vitro. VAL-083 crosses the blood-brain barrier and showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine appropriate VAL-083 dosing for advancement to Phase III trials as a new treatment for recurrent GBM. METHODS: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm, dose-escalation study. Patients received VAL-083 on days 1,2,3 of a 21-day cycle, until reaching MTD. Phase II: Additional patients enrolled at MTD to further assess safety and outcomes. RESULTS: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5-50 mg/m2/d). 40mg/m2/d was confirmed as MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses up to 40mg/m2/d. Dose limiting G4 thrombocytopenia was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related survival improvement was observed. Pharmacokinetic analyses show 1-2h plasma terminal half-life; average Cmax 781ng/mL at 40mg/m2/d. Phase II: 14 patients were enrolled at 40mg/m2/d. To date, safety observations in Phase II are consistent with Phase I. CONCLUSIONS: VAL-083 at 40mg/m2/d exhibits a favorable safety profile and dose-related trend toward clinically meaningful improved survival in refractory GBM patient

The authors used gradual ligamentous distraction for closed reduction of nine irreducible dorsal fracture dislocations of the PIP joint. The volar fragment size was equal to or less than 40% in five and more than 50% in four. The average follow up was 18 months. The sequence of treatment required distraction, translation, and joint flexion. Overdistraction by approximately 2 mm was necessary to get sufficient soft tissue lengthening. This allowed adequate joint flexion for concentric joint reduction. Distraction and simultaneous mobilization restored the final range of motion earlier than distraction and subsequent mobilization. The final range of motion of the PIP and DIP joints was from 12 degrees to 91 degrees and 0 to 45 degrees respectively.

Aung Naing1, Jeffrey R. Infante2, Kyriakos P. Papadopoulos3, Karen A. Autio4, Patrick A. Ott5, Deborah J. Wong6, Gerald S. Falchook7, Manish R. Patel2,8 , Shubham Pant9 and Martin Oft10 1 MD Anderson Cancer Center, Houston, TX; 2 Sarah Cannon Research Institute / Tennessee Oncology, PLLC; 3 START Center for Cancer Care, San Antonio, TX; 4 Memorial Sloan-Kettering Cancer Center, New York, NY; 5 Dana-Farber Cancer Institute, Boston, MA; 6 University of California Los Angeles (UCLA), Los Angeles, CA; 7 Sarah Cannon Research Institute at HealthONE, Denver, CO; 8 Florida Cancer Specialists, Sarasota, FL; 9 Oklahoma University, Oklahoma City, OK; 10 ARMO BioSciences, Redwood City CA

I/sub DDQ/ techniques have been widely used at Intel over the past years to (a) successfully improve outgoing quality of the products by screening defects early in production testing, (b) eliminate or reduce burn in, and (c) improve overall fault grading. Functional (non-scan) I/sub DDQ/ testing has been implemented successfully on a number of products (i960(R), i386/sup TM/EX, and MCS(R) micro-controllers). With more designs implementing scan, the capability to select, grade and implement scan-based I/sub DDQ/ vectors and the resulting contribution to the overall fault coverage can be complicated. Using this I/sub DDQ/ test methodology, we show how to (a) integrate test techniques into the design flow (b) eliminate the need for fault grading, (c) use scan/I/sub DDQ/ to improve fault coverage, and (d) determine the incremental non-scan and scan I/sub DDQ/ coverage impact on the full chip. This paper details the new test technique, methodology, flows, tradeoffs/benefits, implementation, and results for I/sub DDQ/ vector generation, grading, selection and testing of vectors for non-scan and scan-based designs. This technique allows user(s) the option of eliminating comprehensive fault grading resources, and uses existing or new Electronic Design Automation (EDA) tools to achieve desired quality levels prior to design completion, and production testing.

This paper presents an analysis of a circular hollow cylinder composed of strain rate hardening plastic material subjected to a sudden internal pressure loading. Materials satisfying the constitutive relation, σ ∼ = σ 0 ϵ ∼ m and Levy-Mises equation are considered in the analysis. Dynamic and static analyses of axially symmetric material loaded under plane strain condition are described. The paper discusses the effect of strain rate hardening exponent, m , on the dynamic and static plastic response in the axially symmetric medium. A method is presented for the determination of the strain rate hardening exponent by measuring the hoop stress on the outer surface of a thin cylindrical specimen using the static solution.

Existing blending theories have mostly been verified in the past by mixing of monosized, smooth, spherical particles. In this study, binary mixing of non-spherical particles with rough surfaces is shown to adhere to diffusional mixing equations as long as the mean diameters of the two fractions (A and B) are identical, i.e.dA = dB. When this is not the case, blending rates (diffusional coefficients of blending, D) reduce drastically when the small particles are not of such a size that they will fit into the interstices between the larger particles. It is shown also that the final standard deviation in these cases is many orders of magnitude higher than the predicted random standard deviation. When dA = dB, the diffusion coefficient will depend on the magnitude of dA. The diffusion coefficient is not a function of the ratio of A to B. In blending in a horizontal mixer, D decreases with addition of lubricant. This is not the case in a V-blender, where bulk mass transfer appears to be the controlling step. In all other respects, V-blending is identical, functionally, to the profiles obtained in cylindrical blending.

The development is described of a test to measure irradiation enhanced creep in bending of 20% cold-worked Type-316 stainless steel. The test will be irradiated in the experimental fast reactor EBR-II. The rationale used in design selection is described. The selected beam designs, the supportive tests in other stress states and the measurement techniques are described in detail.

An experimental program involving small turn segment models demonstrated the inter-related effects of thermal aging and mechanical stressing on the integrity of transformer conductor insulation. The experimental data was used to develop mathematical relationships between insulation wear life and the thermal and mechanical parameters which influence it. While modeling limitations preclude the use of these relationships for absolute life predictions without further correlating experiments on larger transformer-like structures, the relationships can be applied on a relative basis to answer questions about loading guides and practices and about effects of different magnitudes and numbers of short-circults. Examples of such applications have been given and discussed.

The two-dimensional plane strain equation of plastic flow in accordance with the Levy-Mises constitutive relation is expressed in terms of stress functions of complex variables. Expressions for the stress, strain rate and velocity are derived for plastic flow in a non linear viscous medium assuming the stress function in the form of both the summation and product of conjugate stress functions. The plastic states are derived, also using a mixed mode solution expressed in terms of non-seperable, independent conjugate complex variables. The analysis of the block indentation associated with a nonlinear viscous (strain rate hardening) material under plane strain condition using the product form solution is performed. The effect of the variation in the strain-rate hardening exponent on the contact stress is investigated. The predicted behavior of the vertical component of the contact stress suggests the possibility of the development of a specially instrumented plane strain block indentation tests, for the rapid determination of the strain-rate sensitivity of the real material. The vertical contact stress and strain-rate obtained from the product of the complex conjugate stress function are compared with those obtained from the summation form of the complex conjugate stream function.

Dimeric Cu(II) complexes of thiosemicarbaznes derived from α-oximinoacetoacetanilide (OAATS), α-oximinoacetoacet-o-toluidide (OAOTTS), α-oximinoacetoacet-p-toluidide (OAPTTS), α-oximinoacetoacet-o-anisidide (OAOATS), α-oximinoacetoacet-p-anisidide (OAPATS), α-oximinoacetoacet-o-chloroanilde (OAOCATS), α-oximinoacetoacet-m-chloroanilide (OAMCATS), α-oximinoacetoacet-p-chloroanilide (OAPCATS) and α-oximinoacetoacet-m-(2,4)xylidide (OAMXTS) having general formula [CuL]2 are characterised by elemental analyses, IR, ESR and Reflectance spectra and magnetic susceptibilities. From the IR spectra of the complexes it is concluded that thiosemicarbazones coordinate through oxygen of oximino group and 1-nitrogen and sulphur of of thiosemicarbazide moiety, acting as tridentate ligands. The dimeric nature of the complexes is revealed by lowering in magnetic moments at room temperature (μeff = 1.25–1.51 B.M.). The reflectance and ESR spectra have also been discussed to understand the nature of bonding in the complexes.

Nearly eighty substituted thiocarbanilides–viz., p -(2-thiazolyl)-, p -(4-thiazolyl)- and p -(5-thiazolyl)- p -alkoxy-thiocarbanilides, and p - p ′-bis(4-thiazolyl)-thiocarbanilides, along with a few thiazolyl thiocarbanilides having halogens on the phenyl ring containing the p ′-alkoxy group, have been synthesized and studied for in vitro antitubercular activity. Also described are over 40 new substituted thiazoles prepared as intermediates. p -(4-Thiazolyl)- p ′- alkoxy-thiocarbanilides in general showed the maximum in vitro tuberculostatic activity in the present study. p -(2,5-Dimethyl-4-thiazolyl)- p ′- n -propoxythiocarbanilide had the same in vitro tuberculostatic activity as isonicotinic acid hydrazide ( INH ) (0.04 mcg./ml.) but did not produce tuberculostatic serum concentration at the same oral dose level as INH .